[Cell-biology] Effects of estrogens on irradiated MCF-7 breast
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Tue Mar 6 04:46:46 EST 2007
“Estrogens decrease γ-ray–induced senescence and maintain cell cycle
progression in breast cancer cells independently of p53”
An article by Robert-Alain Toillon (*), Nicolas Magné (§), Ioanna
Laïos (*), Pierre Castadot (§), Eric Kinnaert (§), Paul Van Houtte
(§), Christine Desmedt (#), Guy Leclercq (*), Marc Lacroix (*)(&).
Affiliations: (*) Jean-Claude Heuson Breast Cancer Laboratory, Free
University of Brussels, Brussels, Belgium; (§) Radiotherapy Unit and
(#) Microarray Unit, Jules Bordet Institute, Brussels, Belgium; (&)
InTextoResearch, Baelen, Wallonia, Belgium
in International Journal of Radiation Oncology Biology Physics (2007)
Sequential administration of radiotherapy and endocrine therapy is
considered to be a standard adjuvant treatment of breast cancer.
Recent clinical reports suggest that radiotherapy could be more
efficient in association with endocrine therapy. The aim of this study
was to evaluate the estrogen effects on irradiated breast cancer cells
Methods and Materials:
Using functional genomic analysis, we examined the effects of 17-β-
estradiol (E2, a natural estrogen) on MCF-7 breast cancer cells.
Our results showed that E2 sustained the growth of IR-cells.
Specifically, estrogens prevented cell cycle blockade induced by γ-
rays, and no modification of apoptotic rate was detected. In IR-cells
we observed the induction of genes involved in premature senescence
and cell cycle progression and investigated the effects of E2 on the
p53/p21waf1/cip1/Rb pathways. We found that E2 did not affect p53
activation but it decreased cyclin E binding to p21waf1/cip1 and
sustained downstream Rb hyperphosphorylation by functional
inactivation of p21waf1/cip1. We suggest that Rb inactivation could
decrease senescence and allow cell cycle progression in IR-cells.
These results may help to elucidate the molecular mechanism underlying
the maintenance of breast cancer cell growth by E2 after irradiation-
induced damage. They also offer clinicians a rational basis for the
sequential administration of ionizing radiation and endocrine
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